Oxcarbazepine: structure and anticonvulsant activity

In the crystal structure of the title compound, 10-oxo-10,11-di­hydro-5H-dibenzo­[b,f]­azepine-5-carbox­amide, C₁₅H₁₂N₂O₂, the azepine seven-membered ring adopts a classical but slightly twisted boat conformation, forcing the mol­ecule to adopt a butterfly shape. In addition to one normal hydrogen bond, two non-standard weak hydrogen bonds of the C—H...O type also contribute to the molecular arrangement in the crystal structure. Stereochemical comparison with phenytoin indicates that oxcarbazepine may utilize the same mechanism for its anticonvulsant activity.

Key indicators

• Single-crystal X-ray study
• T = 294 K
• Mean [sigma](C-C) = 0.003 Å
• R factor = 0.037
• wR factor = 0.124
• Data-to-parameter ratio = 9.4

checkCIF/PLATON results

No syntax errors found



Alert level A
PLAT027_ALERT_3_A _diffrn_reflns_theta_full (too) Low ............      64.99 Deg.

Author Response: ...'see _exptl_special_details'

Alert level C
REFNR01_ALERT_3_C  Ratio of reflections to parameters is < 10 for a
            centrosymmetric structure
            sine(theta)/lambda                0.5878
            Proportion of unique data used    1.0000
            Ratio reflections to parameters   9.3756
THETM01_ALERT_3_C  The value of sine(theta_max)/wavelength is less than 0.590
            Calculated sin(theta_max)/wavelength =    0.5878
PLAT023_ALERT_3_C Resolution (too) Low [sin(th)/Lambda < 0.6].....      64.99 Deg.
PLAT088_ALERT_3_C Poor Data / Parameter Ratio ....................       9.38
PLAT420_ALERT_2_C D-H Without Acceptor       N18    -   H182   ...          ?

   1 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   5 ALERT level C = Check and explain
   0 ALERT level G = General alerts; check

   0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   1 ALERT type 2 Indicator that the structure model may be wrong or deficient
   5 ALERT type 3 Indicator that the structure quality may be low
   0 ALERT type 4 Improvement, methodology, query or suggestion

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Computing details

Data collection: Picker Software (Picker, 1967); cell refinement: Picker Software; data reduction: Picker Software; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: SHELXL97.

10-oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide

Crystal data

C15H12N2O2	Dx = 1.380 Mg m^−3
Mr = 252.27	Melting point: not measured K
Monoclinic, P21/c	Cu Kα radiation, λ = 1.54178 Å
a = 5.276 (2) Å	Cell parameters from 32 reflections
b = 9.307 (4) Å	θ = 30–54°
c = 24.841 (7) Å	µ = 0.76 mm^−1
β = 95.64 (2)°	T = 294 K
V = 1213.9 (8) Å^3	Needle, colorless
Z = 4	0.49 × 0.15 × 0.11 mm
F(000) = 528

Data collection

Picker FACS-1 4-circle diffractometer	1761 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.000
Ni-filtered radiation monochromator	θmax = 65.0°, θmin = 3.6°
θ/2θ scan	h = 0→6
Absorption correction: ψ scan (North et al., 1968)	k = −10→0
Tmin = 0.867, Tmax = 0.917	l = −29→28
2072 measured reflections	3 standard reflections every 100 reflections
2072 independent reflections	intensity decay: 0.7%

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.037	All H-atom parameters refined
wR(F^2) = 0.124	w = 1/[σ^2(Fo^2) + (0.1065P)^2 + 0.235P] where P = (Fo^2 + 2Fc^2)/3
S = 0.81	(Δ/σ)max = 0.001
2072 reflections	Δρmax = 0.16 e Å^−3
221 parameters	Δρmin = −0.15 e Å^−3
0 restraints	Extinction correction: SHELXL, Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0115 (12)

Special details

Experimental. PICKER FACS-1 mechanical limit does not allow for data collection above θ = 65° Data were collected on a crystal mounted along its long axis.

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
C1	0.3037 (3)	0.32591 (19)	0.59887 (7)	0.0494 (4)
C2	0.1629 (3)	0.23151 (19)	0.62724 (8)	0.0520 (5)
C3	0.0329 (3)	0.28049 (18)	0.66915 (8)	0.0490 (4)
C4	0.0439 (3)	0.42400 (17)	0.68372 (6)	0.0417 (4)
N5	0.1992 (2)	0.66760 (13)	0.66889 (5)	0.0361 (3)
C6	−0.1250 (3)	0.85135 (16)	0.65407 (7)	0.0413 (4)
C7	−0.2780 (3)	0.94051 (19)	0.62071 (8)	0.0510 (4)
C8	−0.2541 (4)	0.9437 (2)	0.56571 (8)	0.0569 (5)
C9	−0.0790 (4)	0.8566 (2)	0.54463 (7)	0.0529 (5)
C10	0.2732 (4)	0.6800 (2)	0.54995 (7)	0.0500 (4)
C11	0.4531 (3)	0.57875 (18)	0.58142 (7)	0.0470 (4)
C12	0.1871 (3)	0.51694 (16)	0.65566 (6)	0.0356 (4)
C13	0.3158 (3)	0.47037 (17)	0.61289 (6)	0.0403 (4)
C14	0.0547 (3)	0.76342 (15)	0.63302 (6)	0.0361 (4)
C15	0.0821 (3)	0.76539 (17)	0.57731 (6)	0.0419 (4)
C16	0.3440 (3)	0.72171 (15)	0.71368 (6)	0.0355 (4)
O17	0.3538 (2)	0.85078 (11)	0.72298 (5)	0.0450 (3)
N18	0.4735 (3)	0.62560 (17)	0.74566 (6)	0.0521 (4)
O19	0.2846 (4)	0.6952 (2)	0.50180 (6)	0.0858 (5)
H1	0.395 (4)	0.295 (2)	0.5693 (9)	0.070 (6)*
H2	0.152 (4)	0.127 (2)	0.6187 (8)	0.053 (5)*
H3	−0.064 (4)	0.214 (2)	0.6893 (8)	0.057 (5)*
H4	−0.054 (3)	0.4616 (19)	0.7118 (7)	0.044 (4)*
H6	−0.146 (4)	0.848 (2)	0.6927 (8)	0.051 (5)*
H7	−0.403 (5)	1.003 (3)	0.6361 (8)	0.074 (6)*
H8	−0.360 (4)	1.007 (2)	0.5420 (8)	0.064 (6)*
H9	−0.063 (4)	0.857 (2)	0.5074 (10)	0.071 (7)*
H111	0.565 (4)	0.635 (2)	0.6066 (7)	0.045 (5)*
H112	0.561 (4)	0.533 (2)	0.5551 (9)	0.063 (5)*
H181	0.473 (4)	0.534 (2)	0.7402 (8)	0.060 (6)*
H182	0.572 (5)	0.668 (2)	0.7737 (10)	0.069 (6)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0553 (10)	0.0436 (9)	0.0505 (9)	−0.0044 (7)	0.0117 (8)	−0.0149 (7)
C2	0.0594 (11)	0.0356 (9)	0.0605 (11)	−0.0080 (7)	0.0031 (8)	−0.0086 (8)
C3	0.0513 (9)	0.0399 (9)	0.0559 (10)	−0.0104 (7)	0.0057 (8)	0.0046 (8)
C4	0.0445 (8)	0.0422 (9)	0.0395 (8)	−0.0014 (6)	0.0093 (7)	0.0016 (6)
N5	0.0464 (7)	0.0300 (6)	0.0320 (6)	0.0002 (5)	0.0038 (5)	−0.0033 (5)
C6	0.0429 (8)	0.0371 (8)	0.0439 (9)	−0.0012 (6)	0.0047 (7)	−0.0019 (6)
C7	0.0474 (9)	0.0415 (9)	0.0629 (11)	0.0026 (7)	−0.0003 (8)	−0.0008 (8)
C8	0.0582 (10)	0.0489 (10)	0.0601 (11)	0.0003 (8)	−0.0121 (9)	0.0100 (9)
C9	0.0636 (11)	0.0551 (11)	0.0384 (9)	−0.0117 (8)	−0.0021 (8)	0.0099 (8)
C10	0.0596 (10)	0.0550 (10)	0.0373 (8)	−0.0118 (8)	0.0149 (7)	−0.0011 (7)
C11	0.0486 (9)	0.0474 (10)	0.0479 (9)	−0.0067 (7)	0.0192 (8)	−0.0075 (8)
C12	0.0403 (8)	0.0316 (7)	0.0348 (7)	−0.0015 (6)	0.0027 (6)	−0.0031 (6)
C13	0.0426 (8)	0.0385 (9)	0.0407 (8)	−0.0036 (6)	0.0077 (6)	−0.0050 (6)
C14	0.0404 (8)	0.0325 (7)	0.0354 (8)	−0.0066 (6)	0.0037 (6)	0.0003 (6)
C15	0.0481 (9)	0.0415 (8)	0.0362 (8)	−0.0106 (7)	0.0044 (6)	0.0019 (6)
C16	0.0401 (8)	0.0349 (8)	0.0324 (7)	−0.0002 (6)	0.0078 (6)	−0.0026 (6)
O17	0.0544 (7)	0.0348 (6)	0.0450 (6)	−0.0011 (5)	0.0005 (5)	−0.0087 (5)
N18	0.0659 (10)	0.0402 (8)	0.0466 (8)	0.0038 (7)	−0.0122 (7)	−0.0030 (6)
O19	0.1080 (12)	0.1127 (14)	0.0412 (7)	0.0169 (10)	0.0292 (8)	0.0072 (8)

Geometric parameters (Å, º)

C1—C13	1.389 (2)	C8—C9	1.371 (3)
C1—C2	1.387 (3)	C8—H8	0.97 (2)
C1—H1	0.96 (2)	C9—C15	1.402 (2)
C2—C3	1.379 (3)	C9—H9	0.94 (2)
C2—H2	0.99 (2)	C10—O19	1.212 (2)
C3—C4	1.384 (2)	C10—C15	1.499 (2)
C3—H3	0.97 (2)	C10—C11	1.501 (3)
C4—C12	1.381 (2)	C11—C13	1.505 (2)
C4—H4	0.974 (19)	C11—H111	0.971 (19)
N5—C16	1.3812 (19)	C11—H112	1.00 (2)
N5—C14	1.4271 (19)	C12—C13	1.385 (2)
N5—C12	1.4402 (19)	C14—C15	1.406 (2)
C6—C7	1.377 (2)	C16—O17	1.2234 (18)
C6—C14	1.393 (2)	C16—N18	1.338 (2)
C6—H6	0.98 (2)	N18—H181	0.86 (2)
C7—C8	1.385 (3)	N18—H182	0.92 (2)
C7—H7	0.99 (2)
C13—C1—C2	119.96 (16)	O19—C10—C15	119.14 (18)
C13—C1—H1	117.8 (14)	O19—C10—C11	119.80 (18)
C2—C1—H1	122.2 (14)	C15—C10—C11	121.05 (14)
C3—C2—C1	120.34 (16)	C10—C11—C13	112.29 (14)
C3—C2—H2	117.4 (12)	C10—C11—H111	108.1 (11)
C1—C2—H2	122.3 (12)	C13—C11—H111	108.6 (11)
C2—C3—C4	120.35 (16)	C10—C11—H112	107.2 (12)
C2—C3—H3	120.1 (12)	C13—C11—H112	112.8 (12)
C4—C3—H3	119.6 (12)	H111—C11—H112	107.6 (16)
C12—C4—C3	118.92 (15)	C4—C12—C13	121.63 (14)
C12—C4—H4	119.5 (11)	C4—C12—N5	120.58 (13)
C3—C4—H4	121.5 (11)	C13—C12—N5	117.75 (13)
C16—N5—C14	119.62 (12)	C1—C13—C12	118.78 (14)
C16—N5—C12	123.18 (12)	C1—C13—C11	122.08 (15)
C14—N5—C12	117.20 (12)	C12—C13—C11	119.07 (14)
C7—C6—C14	120.58 (16)	C6—C14—C15	120.10 (14)
C7—C6—H6	119.5 (11)	C6—C14—N5	118.33 (13)
C14—C6—H6	119.9 (11)	C15—C14—N5	121.50 (13)
C8—C7—C6	120.13 (17)	C9—C15—C14	117.58 (16)
C8—C7—H7	119.9 (13)	C9—C15—C10	117.06 (15)
C6—C7—H7	120.0 (13)	C14—C15—C10	125.35 (15)
C7—C8—C9	119.63 (17)	O17—C16—N18	122.31 (15)
C7—C8—H8	120.6 (12)	O17—C16—N5	121.32 (13)
C9—C8—H8	119.8 (12)	N18—C16—N5	116.37 (14)
C8—C9—C15	121.96 (17)	C16—N18—H181	125.0 (14)
C8—C9—H9	120.1 (14)	C16—N18—H182	112.6 (14)
C15—C9—H9	118.0 (14)	H181—N18—H182	122 (2)
C13—C1—C2—C3	0.5 (3)	C10—C11—C13—C12	−67.2 (2)
C1—C2—C3—C4	−0.7 (3)	C7—C6—C14—C15	0.2 (2)
C2—C3—C4—C12	−0.1 (3)	C7—C6—C14—N5	−176.79 (14)
C14—C6—C7—C8	−0.1 (3)	C16—N5—C14—C6	−57.77 (19)
C6—C7—C8—C9	0.6 (3)	C12—N5—C14—C6	122.83 (15)
C7—C8—C9—C15	−1.3 (3)	C16—N5—C14—C15	125.26 (15)
O19—C10—C11—C13	−126.31 (19)	C12—N5—C14—C15	−54.15 (19)
C15—C10—C11—C13	54.9 (2)	C8—C9—C15—C14	1.4 (3)
C3—C4—C12—C13	1.1 (2)	C8—C9—C15—C10	−177.44 (16)
C3—C4—C12—N5	178.74 (14)	C6—C14—C15—C9	−0.9 (2)
C16—N5—C12—C4	76.37 (19)	N5—C14—C15—C9	176.07 (14)
C14—N5—C12—C4	−104.25 (16)	C6—C14—C15—C10	177.88 (15)
C16—N5—C12—C13	−105.92 (17)	N5—C14—C15—C10	−5.2 (2)
C14—N5—C12—C13	73.46 (18)	O19—C10—C15—C9	1.6 (3)
C2—C1—C13—C12	0.6 (3)	C11—C10—C15—C9	−179.64 (15)
C2—C1—C13—C11	−176.36 (17)	O19—C10—C15—C14	−177.16 (18)
C4—C12—C13—C1	−1.4 (2)	C11—C10—C15—C14	1.6 (2)
N5—C12—C13—C1	−179.04 (14)	C14—N5—C16—O17	−0.9 (2)
C4—C12—C13—C11	175.65 (15)	C12—N5—C16—O17	178.42 (14)
N5—C12—C13—C11	−2.0 (2)	C14—N5—C16—N18	179.68 (14)
C10—C11—C13—C1	109.72 (18)	C12—N5—C16—N18	−1.0 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N18—H181···O17^i	0.86 (2)	2.10 (2)	2.800 (2)	137.7 (18)
C1—H1···O19^ii	0.96 (2)	2.56 (2)	3.475 (2)	158.4 (18)
C4—H4···O17^iii	0.974 (19)	2.587 (18)	3.346 (2)	134.9 (13)

Symmetry codes: (i) −x+1, y−1/2, −z+3/2; (ii) −x+1, −y+1, −z+1; (iii) −x, y−1/2, −z+3/2.